Continuation of Vibrational Optical Activity studies of proteins, peptides and nucleic acids with an emphasis on applications of vibrational circular dichroism (VCD) to structural analysis are proposed. Systematic interpretation of VCD data coupled to data from other spectroscopic techniques employing statistically based models will be used to refine the information obtainable from spectroscopic studies of such molecules. VCD samples the chiral nature of localized transitions of a biomolecule in its ground electronic state and yields data shown to be highly sensitive to structural variation. Statistical data analysis algorithms developed for protein spectral analysis have demonstrated an ability to predict secondary structure from spectra that in some cases has an advantage over conventional electronic CD and FTlR based techniques. Coupling all of this spectral information can lead to its more reliable application. Specifically the project will entail: 1. VCD instrumental development to improve sensitivity through use of step-scan FTlR techniques. This will include extension of the data base to include protein spectra in 1-120 solution, avoiding the need for deuterium exchange. 2. Analysis of segment length, folding pattern and environmental effects on the observed spectra. 3. Neural network analysis of spectra in terms of structure using both secondary structure descriptors and environmental aspects (such as folding patterns). 4. Study of specific protein conformational problems related to the folding problem. 5. Study of the spectral character of model peptide systems to gain insight into the origin of the more complex bandshapes seen in protein spectra and application to oxytocin derivatives. 6. Theoretical simulation of peptide and protein VCD using quantum mechanical evaluation of near-neighbor interactions and dipolar modeling of long range interactions. 7. Determination of specific characteristic spectral forms for uniquely folded nucleic acid structures.